FIGURE

Fig. 4

ID
ZDB-FIG-160707-39
Publication
Lisse et al., 2016 - Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebrafish
Other Figures
All Figure Page
Back to All Figure Page
Fig. 4

Paclitaxel-induced neurotoxicity in larval fish is attenuated by MMP-13 inhibition. (A and B) Cutaneous branches of a single-labeled RB neuron were traced for 12 h in the caudal fin following fin amputation. Larvae were incubated for 3 h either in vehicle solution (0.5% DMSO/Ringers) (A) or paclitaxel (22 µM) (B). Insets show higher magnification of boxed regions (arrowheads depict axon debris lost in vehicle but not paclitaxel-treated animals). Tracks in the last panel depict branch growth over time. (C) Quantification of mean axon branch growth over 12 h in larvae incubated in vehicle, paclitaxel (22 µM), and paclitaxel plus either DB04760 or CL-82198 (10 µM each) (n = 3, 3-4 fish per group). (D) Comparison of mean axon growth and retraction in injured vehicle and paclitaxel-treated animals over 12 h (n = 2, 3-4 fish and 15 axons per group). (E) Quantification of axon debris clearance (n = 2, 3-4 fish and 5-7 axons per group). (F) Scheme of compound screening assay. (G) Chemical structures of MMP-13 inhibitors. CL-82198, N-[4-(4-morpholinyl)butyl]-2-benzofurancarboxamide; DB04760, N4,N6-bis[(4-fluoro-3-methylphenyl)methyl] pyrimidine-4,6-dicarboxamide. (H) Axon regeneration is partially restored with 10 µM DB04760 (arrowheads mark diminishing axon debris). (I) Comparison of axon branch density following 96 h of treatment (n = 2, 5 fish per group). (J) Touch response in fin and head region after 96 h of treatment (n = 4, 5 fish per group). (K) Percentage of animals with improved touch response upon coadministration of paclitaxel and either CL-82198 or DB04760. *P < 0.05, **P < 0.01, ***P < 0.001. (Scale bar, 50 µm.) hpa, hours postamputation; Pctx, paclitaxel.

Expression Data

Expression Detail
Antibody Labeling
Phenotype Data

Phenotype Detail
Acknowledgments
This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ Proc. Natl. Acad. Sci. USA